文章：

叉头盒蛋白（Fox）在癌症中的新作用

The emerging roles of forkhead box (Fox) proteins in cancer

原文发布日期：2007-11-01

DOI: 10.1038/nrc2223

类型: Review Article

开放获取: 否

要点：

1. Forkhead box (Fox) proteins are a superfamily of evolutionarily conserved transcriptional regulators, which are characterized by the forkhead DNA binding domains, and control a wide range of biological processes.
2. Fox proteins can both activate and repress gene expression through the recruitment of co-factors or repressors, primarily histone deacetylases (HDACs). In addition, Fox proteins interact extensively with other factors such as p53 and oestrogen receptor to modulate gene expression, and deregulation of Fox protein activity or expression results in changes in both direct and indirect target genes.
3. Fox proteins are largely deregulated through genetic events and alterations in post-translational modifications. Post-translational control of Fox protein activity is exerted through an intricate balance of phosphorylation, acetylation and mono-ubiquitylation that influences protein interactions and sub-cellular localization.
4. Deregulation of Fox proteins is commonly associated with tumorigenesis and cancer progression; Fox proteins may be directly targeted or deregulated by mutations in upstream factors.
5. Overexpression of FOXM1 promotes cell-cycle progression, and overexpression of FOXC2 promotes tumour metastasis and invasion. By contrast, loss of FOXO3A activity may increase resistance to apoptosis and cell-cycle progression, and deregulation of FoxP family members can result in tumour immune evasion.
6. Fox proteins may act as both direct and indirect targets for therapeutic intervention. However, the complex nature of Fox transcription factor signalling and their roles as both tumour suppressors and oncogenes makes them challenging therapeutic targets.

要点翻译：

1. 叉头框（Fox）蛋白是一个进化上保守的转录调控因子超家族，其特征是具有叉头状DNA结合结构域，并调控广泛的生物学过程。
2. Fox蛋白通过招募辅因子或抑制因子（主要是组蛋白去乙酰化酶）既可激活也可抑制基因表达。此外，Fox蛋白与p53和雌激素受体等其他因子广泛相互作用以调节基因表达，而Fox蛋白活性或表达的失调会导致直接和间接靶基因的变化。
3. Fox蛋白的失调主要源于遗传事件和翻译后修饰的改变。Fox蛋白活性的翻译后调控通过磷酸化、乙酰化和单泛素化的复杂平衡来实现，这些修饰影响蛋白质相互作用和亚细胞定位。
4. Fox蛋白的失调通常与肿瘤发生和癌症进展相关；Fox蛋白可能直接被靶向或通过上游因子的突变而失调。
5. FOXM1的过表达促进细胞周期进程，FOXC2的过表达促进肿瘤转移和侵袭。相比之下，FOXO3A活性的丧失可能增加对凋亡的抵抗和细胞周期进程，而FoxP家族成员的失调可能导致肿瘤免疫逃逸。
6. Fox蛋白可能作为治疗干预的直接和间接靶点。然而，Fox转录因子信号传导的复杂性及其既作为肿瘤抑制因子又作为癌基因的作用，使它们成为具有挑战性的治疗靶点。

英文摘要：

Forkhead box (Fox) proteins are a superfamily of evolutionarily conserved transcriptional regulators, which control a wide spectrum of biological processes. As a consequence, a loss or gain of Fox function can alter cell fate and promote tumorigenesis as well as cancer progression. Here we discuss the evidence that the deregulation of Fox family transcription factors has a crucial role in the development and progression of cancer, and evaluate the emerging role of Fox proteins as direct and indirect targets for therapeutic intervention, as well as biomarkers for predicting and monitoring treatment responses.

摘要翻译： 

叉头框（Fox）蛋白是一类进化上保守的转录调控因子超家族，控制着广泛的生物学过程。因此，Fox功能的缺失或获得可改变细胞命运，促进肿瘤发生及癌症进展。本文探讨证据表明Fox家族转录因子的失调在癌症的发生与进展中起关键作用，并评估Fox蛋白作为治疗干预的直接和间接靶点，以及用于预测和监测治疗反应的生物标志物的新兴角色。

原文链接：

The emerging roles of forkhead box (Fox) proteins in cancer